Lomeguatrib (192441-08-0) is a potent (IC50 = 9 nM) inhibitor of O6-Methylguanine-DNA Methyltransferase (MGMT), an important DNA repair protein.1 It is currently being investigated in cancers that have acquired resistant to the chemotherapeutic temozolomide2-5, as well as other chemotherapeutics6,7.
1) Reinhard et al. (2001), Monosaccharide-Linked Inhibitors of O6-Methylguanine-DNA Methyltransferase (MGMT): Synthesis, Molecular Modeling, and Structure-Activity Relationships; J. Med. Chem. 44 4050
2) Barvaux et al. (2004), Sensitization of a human ovarian cancer cell line to temozolomide by simultaneous attenuation of the Bcl-2 antiapoptotic protein and DNA repair by O6-alkylguanine-DNA alkyltransferase: Mol. Cancer Ther. 3 1215
3) Gumbrell et al. (2006), Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors: Clin. Cancer Res. 12 1577
4) Watson et al. (2009), O(6)-methylguanine-DNA methyltransferase depletion and DNA damage in patients with melanoma treated with temozolomide alone or with lomeguatrib: Br. J. Cancer 100 1250
5) Taspinar et al. (2013), Effect of lomeguatrib-temozolomide combination of MGMT promoter methylation and expression in primary glioblastoma tumor cells: Tumour Biol. 34 1935
6) Sabharwal et al. (2010), A phase I trial of lomeguatrib and irinotecan in metastatic colorectal cancer: Cancer Chemother. Pharmacol. 66 829
7) Tawbi et al. (2011), Inhibition of DNA repair with MGMT pseudosubstrates: phase I study of lomeguatrib in combination with dacarbazine in patients with advanced melanoma and other solid tumors: Br. J. Cancer 105 773